Smart Plasmonic Nanozyme Enhances Combined Chemo-photothermal Cancer Therapy and Reveals Tryptophan Metabolic Apoptotic Pathway

Abstract

Regulation of the tumor microenvironment is considered to be an intelligent strategy for cancer therapeutics, but the related metabolic pathways of cell apoptosis still remain a great challenge. Herein, by applying multifunctional carbon dot-decorated Ag/Au bimetallic nanoshells (CDs-Ag/Au NSs, CAANSs) nanoprobes as smart plasmonic nanozymes for combined chemo-photothermal cancer therapy, we achieved a high efficiency in cancer cell therapy and revealed a tryptophan (Trp) metabolic apoptotic pathway. In addition to high photothermal conversion efficiency, the CAANSs can act as a smart nanozyme to catalyze intracellular H2O2 to the cytotoxic reactive oxygen species (ROS) of superoxide anion (·O2-), in response to mild acidic cancerous cell microenvironment to damage cellular DNA. More importantly, the Trp metabolic pathway during the combined chemo-photothermal therapy has revealed that the Trp participates in an oxidative stress process, which can be decomposed to produce H2O2 and further formed into superoxide anions to kill cells under the catalytic nanomedicine process. The current work provides an effective platform for cancer therapeutics and is promising for cancer-related molecular biology studies.